Enzymatic Deacylation of Mono- and Dibutyryl Derivatives of Cyclic Adenosine 3′, 5′-Monophosphate by Extracts of Rat Tissues

Cell-free extracts of several rat tissues contained N6-butyryl amidohydrolase and O2'-butyryl esterase activities for the deacylation of [3H]butyryl-labeled N6, O2'-dibutyryl cyclic AMP, N6-monobutyryl cyclic AMP, and O2'-monobutyryl cyclic AMP. The highest rates of deacylation were in the soluble cytoplasm of all tissues; cyclic AMP phosphodiesterase activities were also highest in the same cell compartment. Since rates of cyclic AMP phosphodiesterase and 5'-AMP 5'-nucleotidase activities were from one to two orders of magnitude greater than those of the deacylases, deacylation is clearly the rate-limiting process in the catabolism of butyryl derivatives of cyclic AMP to adenosine. Despite these relatively low rates of deacylation, they are sufficiently high to produce, even when operating minimally, amounts of cyclic AMP far greater than could be produced endogenously, even under hormonal stimulation. It is concluded that dibutyryl cyclic AMP could serve as a source of intracellular cyclic AMP and of biologically active monobutyryl cyclic AMP.